Author + information
- William R. Davidson Jr., MDa,∗ (, )@PennStHershey@BWHResearch and
- Ada C. Stefanescu Schmidt, MD, MScb@DrAdaStefanescu
- aProgram for Adult Congenital Heart Disease, Heart and Vascular Institute, Pennsylvania State University College of Medicine, Hershey, Pennsylvania
- bDepartment of Cardiology, Boston Children’s Hospital, Cardiovascular Division, Brigham and Women’s Hospital, and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. William R. Davidson, Jr., Cardiology H047, 500 University Drive, Hershey, Pennsylvania 17033.
Percutaneous placement of a bioprosthetic pulmonic valve in 2000 (1) ushered in the era of transcatheter valve placement. In congenital heart disease patients, especially adolescents and adults, a nonsurgical approach to managing severe pulmonic insufficiency received ready acceptance. Reduced acute morbidity and longer intervals between sternotomies were considered key advantages. Long-term outcome comparisons with surgical pulmonary valve replacement remain lacking. Reports of infective endocarditis (IE) (2,3) in the Melody (Dublin, Ireland) transcatheter pulmonary valve replacement (TPVR) raised safety concerns about the TPVR approach.
In this issue of the Journal, McElhinney et al. (4) have extended their 2013 analysis of 3 industry-sponsored registries of the TPVR (2) to include 1,660.3 patient-years of observation, (median follow-up 5.1 years). A supplemental questionnaire added in 2013 provided more information on IE risk factors, diagnosis, and outcomes. In 309 patients age 7 to 59 years, 46 episodes of endocarditis occurred with an annualized incidence of 3.1%/patient-year; 35 (2.4%/patient-year) were considered TPVR-related. The 1- and 5-year freedom from IE was 97% and 89%, respectively, with most IE occurring well after implantation. Two independent risk factors for IE were identified: age <12 years at implant (hazard ratio: 2.3) and post-deployment catheter right ventricular outflow tract (RVOT) gradient ≥15 mm Hg (hazard ratio: 2.7). Of the 46 cases, 20% subsequently underwent catheter intervention, and 33% surgical explantation; 5 deaths were attributed to endocarditis (11%), of which 4 had staphylococcal infection.
Site investigators noted difficulty establishing the diagnosis of IE using the modified Duke criteria for IE (5). Establishing evidence of endocardial involvement of the TPVR was the challenge and was done at the sites’ discretion. Transthoracic echocardiography was primarily employed, transesophageal echocardiography only infrequently. Rarely, intracardiac echocardiography, chest computed tomography, 18F-fluorodeoxyglucose position emission tomography, surgical inspection, or pathology from explanted valves were used. TPVR-related IE can present unique imaging challenges due to its location in the lateral or far fields of the 2-dimensional echocardiographic sector. Conduits and stents surrounding the prostheses may further degrade echocardiographic imaging of the leaflets. Nonetheless, transesophageal echocardiography was likely under-utilized (15 of 46 cases) given the large, mobile vegetations seen in Melody IE (4,6,7). There was no core laboratory or central adjudication; site investigators’ diagnoses of IE were the basis for data analysis.
Imaging, surgical, pathological, and other findings from cases were subsequently reviewed by the authors. Of the 34 cases reported as TPVR-related by sites, 8 (24%) were not found to have objective evidence of TPVR involvement, while 33% (4 of 12) classified as non–TPVR-related by sites had evidence of TPVR involvement on review. Sites could be asked by the sponsor to provide more information or modify the diagnosis, but such revisions could not be mandated. After reclassification of the cases, freedom from TPVR-related IE was 99% at 1 year and 94% at 5 years. Clear well-adjudicated prosthetic valve imaging protocols should be included in future TPVR registries; transesophageal echocardiography (6,7) should be included. Systematic application of other valve imaging approaches, such as intracardiac echocardiography and computed tomography (8,9), used by the investigators would be reasonable when echocardiography fails to detect TPVR vegetations.
The lower incidence of TPVR-related IE after the authors’ review puts its risk in a better light, but raises questions concerning the diagnostic criteria used. Of 27 cases of TPVR-related IE, 18 had vegetations, of whom one-half also had RVOT obstruction; RVOT obstruction was the sole evidence of endocardial involvement in the remaining cases, and was more prevalent than in the 2013 report (2). Significant RVOT obstruction at the time of suspected endocarditis was considered to satisfy the modified Duke criteria for endocardial involvement, but acute valve obstruction is not included in the modified Duke criteria (5,6).
Acute TPVR obstruction with life-threatening hemodynamic consequences was a striking feature of this series. Rapidly progressive stenosis is a rare complication of bioprosthetic IE of other valves, but is reported in prosthetic pulmonic IE in valves from several manufacturers (7). McElhinney et al. (4) had sufficient data to classify the cases and propose an approach proportionate to illness severity. Fast action by the site investigators averted the life-threatening consequences of acute right ventricular pressure overload, for which that chamber is typically ill-prepared. Clinicians should be prepared to recognize and act expeditiously to address this unusual and now better described hemodynamic syndrome. Such dramatic cases may have led to the inclusion of significant RVOT obstruction as a marker for TPVR-related IE. Uncharacteristically, acute RVOT obstruction was often associated with Strep species endocarditis, a bacterial family not known for large vegetations. Perhaps the authors have conflated 2 distinct problems: endocarditis and rapid failure of a bioprosthesis? Bioprostheses have much poorer durability in children than in adults, especially after 5 years (10,11). Can a TPVR be expected to be more durable in a child than a surgical bioprosthesis? Perhaps some of these cases did not have TPVR-related IE, rather a rapidly failing bioprosthetic valve and sepsis; interestingly, 83% of patients did not have pre-stenting prior to TPVR deployment, which has been recognized as a risk factor for earlier TPVR obstruction. Progressive stenotic valve failure could have been unmasked by high cardiac output in sepsis. Considering rapidly progressive RVOT stenosis as a criterion for TPVR involvement could result in the overdiagnosis of IE with reduced specificity, as suggested by the authors’ review of the cases. The frequency of catastrophic RVOT obstruction raises new questions about the durability and long-term utility of this ground-breaking bioprosthesis, especially in children. Are there unique anatomic and hemodynamic features of the RVOT that increase the risk of rapidly progressive obstruction in both surgical PVR and TPVR?
The authors have increased our understanding of IE of the valve. A serious hemodynamic syndrome has been better described, but new questions have been raised. Rapid application of new techniques to treat congenital heart disease is often justified by urgent need and the lack of sufficient patients for large trials. This approach has not consistently benefited patients. Years may be necessary to place a therapy in its proper place in the therapeutic armamentarium.
The partnership among clinicians, investigators, and industry demonstrated here is crucial to progress in rapidly evolving but smaller clinical fields such as congenital heart disease. Partnerships with registries designed for quality improvement and research, such as the American College of Cardiology National Cardiovascular Data Registry-IMPACT and the Transcatheter Valve Therapy registries, would enhance collection of high-quality data. Mechanisms to cross-link these registries, with tools and funding to centrally adjudicate imaging findings and case definitions, are next and necessary steps for the field of congenital and structural interventions.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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